Discovering a new therapy is no easy task, and Esther Martinborough, executive director of research at Celgene, knows this firsthand. In 2008, she saw Receptos’ two therapeutic candidates for cancer fail before her team rallied to identify a potential new treatment option for multiple sclerosis (MS). Aided by the 2015 acquisition of Receptos by Celgene, her team is committed to bringing this potential new treatment option to MS patients.
In this Q&A, Martinborough explains that the company’s quick turnaround was due to two factors: the right team and a smarter way to screen therapeutic candidates.
ESTHER MARTINBOROUGH (FAR LEFT) EXECUTIVE DIRECTOR OF RESEARCH AT CELGENE< AND HER COLLEAGUES REVIEW DATA REGARDING THE COMPANY’S THERAPEUTIC CANDIDATE FOR MS.
What was Receptos’ original focus?
When the company was founded in 2008, we were called Apoptos and were focused on several exciting opportunities to develop anticancer therapies. After six months of preclinical research, it became apparent that we could not move forward. The scientific rationale was not holding together, and we explained this to our investors. Fortunately, our investors recognized we had a very qualified team with multiple individuals who had brought treatments to the market successfully. Based on that expertise, our investors put their trust in us and gave us another chance, so we worked as a team to carefully make sure our next hypotheses had the best chances of getting to the clinic. We were thorough, looking closely at multiple compounds and how they worked. We looked at a wide variety of candidates that were scientifically interesting.
Why did you choose to focus on a sphingosine-1-phosphate (S1P) modulator for MS?
There was a good biological rationale. Other S1P modulators were already in the clinic for MS, so we knew it could work. While the S1P compounds we evaluated weren’t quite ready for the clinic, we saw an opportunity to get them there quickly.
The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path.
How long has the development process taken?
We started working on our S1P modulator in March 2009 and were in the clinic less than two years later, which is quite simply astounding. When we began developing S1P modulators, about 20 other companies were ahead of us. Today, we’re one of the leaders in the pack.
How did you accelerate the development?
The difference was our screening approach. Most companies move step-by-step in screening candidates: they test the efficacy and then move onto studying the side effects and toxicology. We consolidated these steps into just one experiment. Using a biomarker for S1P as a preclinical measure of efficacy and lung weight in an animal model to measure safety, we were able to pick the therapeutic candidates with the right potential balance of efficacy and safety quickly.
ESTHER MARTINBOROUGH (RIGHT) AND A COLLEAGUE AT CELGENE DISCUSS THE CHEMICAL STRUCTURE OF THE COMPANY’S S1P MODULATOR THAT IS CURRENTLY IN CLINICAL DEVELOPMENT FOR MS.
What made this S1P modulator stand out from the others being developed?
The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path because that would likely only lead to the same safety and efficacy profiles. Instead, we designed chemical structures in our S1P modulator that were different from those already reported. We looked to map out a unique chemical space that could benefit MS patients.
Learn more about the role of S1P signaling molecules in MS and other immune-inflammatory diseases, read “Corralling White Blood Cells to Rein in Multiple Sclerosis.”
— Celgene Corporation (@Celgene) September 16, 2016